Pathophysiology of Diabetes

**3**

**1. Introduction**

**Chapter 1**

**Abstract**

Pathophysiologic Approach to

Centre Experience 1980–2020

*Rudolf Chlup, Richard Kaňa, Lada Hanáčková,* 

*Hana Zálešáková and Blanka Doubravová*

Type 2 Diabetes Management: One

This overview summarizes the evolution of pathophysiologic treatment of diabetes type 2 (T2D) in the period of the last 40 years. Randomized Controlled Trials (RCT) and Real World Evidence (RWE) studies resulted in recent Statements of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) in the year 2020. Case reports and studies of a single-centre in Czech Republic are reported. The authors demonstrate the impact of (1) multiple doses of rapid insulin, (2) multiple doses of rapid or ultrarapid insulin analogs (3) continuous subcutaneous insulin infusion (CSII) (4) incretin receptor agonists, (5) fixed combination of insulin degludec with liraglutide (IDegLira) and (6) SGLT2 inhibitor dapagliflozin, on plasma glucose concentration, HbA1c, body mass and patient satisfaction. The importance of therapeutic patients' education and technology (personal glucometers, continuous/flash glucose monitors, insulin pens/pumps) is emphasized. Most of the observations were already published. Hence, individually adopted education, lifstyle, technical equipment, incretin receptor agonists and/or metformin and/or gliflozins and/or insulin analogs appear to be the core of an effective pathophysiologic approach. Scientific conclusions from RCTs, RWE trials and own clinical case reports may prevail over clinical inertia and induce early implementation of effective methods into routine T2D treatment.

**Keywords:** insulin analogs, incretins, gliflozins, insulin pen, CSII, glucose monitoring, education, case report, randomized control trial, real world evidence

are induced by different genetic and environmental factors. [2, 3]

Type 2 diabetes mellitus (T2D) is a syndrome of disturbed metabolic pathways of sacharides (carbohydrates), proteins and fat due to various influence of eight pathophysiologic mechanisms described as ominous octet: disturbed dynamics of insulin secretion, reduced production of incretins in gut, hyperglucagonaemia, increased production of glucose from liver, disturbed endocrine function of adipose tissue, insulin resistance, increased activity of sodium glucose transporter 2 (SGLT2) resulting in increased reabsorption of glucose from renal tubules and malfunction of hypothalamic centers for satiety and hunger. [1] These mechanisms

In previous centuries, clinical symptoms of T2D lead to therapeutic attempts

based on lifestyle, diet and on oral antidiabetic drugs, mostly sulfonylureas.
